William & Mary held people enslaved from its inception to the Emancipation Proclamation. The enslaved were an integral part to the university's every day operations. Additionally, the enslaved worked on Nottoway Plantation, which was owned by William & Mary for several years. The profits collected from the labor these individuals at the Nottoway Quarter funded scholarships for the white male students at William & Mary.

Leading up to, during, and after the Civil War, William & Mary employed free people of African descent as well. George Greenhow worked as a janitor throughout the antebellum years. Greenhow called himself the "the only negro educated William & Mary" because he was taught how to read and write by a student.

Henry Billups worked for the university for over fifty years, in a multitude of different capacities, including as a mentor to the young white men who attended the university. He rang the Wren bell alongside President Benjamin Ewell and is uniquely known for procuring alcohol for students and faculty alike during prohibition. Billups worked for William & Mary from 1888-1952, a time marked by Jim Crow and Massive Resistance.

In 1914, formerly enslaved author and activist Booker T. Washington addressed the university community in the Wren Chapel.

During the Spring of 2018, William & Mary erected a plaque at the Wren Building to honor the first three African Americans in residence at the university: Lynn Briley, Janet Brown Strafer and Karen Ely.